Project description
Targeting cancer metabolism as a novel immunotherapeutic strategy
Tumour immune surveillance is hampered by a hostile tumour microenvironment that perturbs the functions of infiltrating effector cells. The EU-funded STIMUNO project has identified a new tumour metabolite that inhibits immune cells and their ability to kill cancer cells. Moreover, the project will study which enzymes in cancer cells are responsible for the production of this inhibitory metabolite. The idea is to propose novel therapeutic modalities targeting this metabolite to overcome the associated immunosuppression. The work will provide fundamental insight into metabolic pathways that are implicated in the regulation of antitumour immune responses.
Objective
The main goal of this project is to explore new fundamental pathways involved in the regulation of antitumor immune response. Since the immunosuppressive tumor microenvironment constitutes a key barrier to effective immunotherapy, our predominant ambition is to characterize novel, hitherto unknown metabolic changes that can support the survival of tumor cells and the escape from the immune surveillance.
We have recently discovered a new metabolite within tumor microenvironment with a robust ability to inhibit the activity of immune cells and their potential to kill target tumor cells. Within the project, we plan to corroborate on our preliminary findings in order to establish the role of this factor in mitigating antitumor immune response. To this end, we will determine the level of its production within tumors in murine models. Moreover, we will relate these findings to human data by analysing the immune milieu and the expression of enzymes involved in generation of this metabolic agent in a cohort of cancer patients. We will also investigate the mechanisms by which this factor could perturb the functions of tumor-infiltrating effector cells.
Finally, we aspire to use the knowledge gained during the implementation of this project to propose innovative therapeutic solutions. Specifically, we will investigate whether and how the inhibition of selected enzymes involved in the generation of this new metabolic checkpoint can impact on the efficacy of immunotherapeutic agents, including immune checkpoint inhibitors, arginase inhibitors as well as adoptive therapy with CAR-T cells and CAR-NK cells. We strongly believe that by achieving the goals of our project we will make a significant step forward in order to develop and to design cutting-edge therapeutic strategies. These compelling solutions would further improve the efficacy of tumor immunotherapy, thus contributing to a breakthrough advance in cancer treatment.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
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Funding Scheme
ERC-STG - Starting GrantHost institution
02 106 WARSZAWA
Poland